Early expression and high prevalence of islet autoantibodies for DR3/4 heterozygons and DR4/4 homozygous offspring of parents with Type I diabetes: The German BABYDIAB study
M. Schenker et al., Early expression and high prevalence of islet autoantibodies for DR3/4 heterozygons and DR4/4 homozygous offspring of parents with Type I diabetes: The German BABYDIAB study, DIABETOLOG, 42(6), 1999, pp. 671-677
Aims/hypothesis. Islet autoantibodies precede the clinical onset of Type I
(insulin-dependent) diabetes mellitus. The cumulative development of such a
utoantibodies in infants followed from birth and in particular infants with
high-risk HLA genotypes is poorly defined, but such information is essenti
al to design trials to prevent islet autoimmunity.
Methods. HLA genotypes were determined in offspring of parents with Type I
diabetes who were followed from birth for at least 2 years (median followup
: 3.1 years) and who were characterised for the expression of insulin, GAD6
5, IA-2 and islet cell autoantibodies at birth, 9 months, 2 and 5 years of
age.
Results. The HLA genotypes DRB1*03/04(DQB1*57non-Asp) and DRB1*04/04(DQB1*5
7non-Asp) were present in 7.1 % and 5.0 % of offspring of parents with Type
I diabetes. The frequency of both genotypes was increased in offspring who
developed islet autoantibodies within the first 2 years of life (27.3 % vs
5.5 %, odds ratio 6.3 [p = 0.002] and 22.7 % vs 4.2 %, odds ratio 6.6 [p =
0.003]) and half of all offspring who developed antibodies had these genot
ypes. Other genotypes were not associated with an increase in risk. By life
-table analysis, the cumulative risk of developing islet autoantibodies by
the age of 2 years was 20 % (95 % CI 9.4,30.6) for offspring carrying eithe
r the DRB1*03/04(DQB1 *57non-Asp) or the DRB1*04/04(DQB1*57non-Asp) genotyp
e compared with 2.7 % (95 % CI 1.2,4.2) for offspring without these genotyp
es (p < 0.0001).
Conclusion/interpretation. These data show that early appearance of islet a
utoantibodies is remarkably frequent for DR3/4 heterozygous and DR4/4 homoz
ygous offspring and indicate that primary prevention could be considered on
ce available in an offspring cohort selected for these genotypes.